The Inheritance Angle: A Determinant for the Number of Members in the Substituted Cucurbit[n]uril Family

Abstract

Two new glycoluril diethers have been prepared, bearing strained cyclobutene and cyclobutane rings at the fused junction of the two imidazolidinone rings. The wide angle of the concave face of the cyclobutano derivative enabled the synthesis of cyclobutanocucurbit[5-8]uril, the largest member being the most significant achievement. A limited binding affinity study compared the new substituted family to classical cucurbit[5-8]uril. Surprisingly lower affinities were found, except for cyclobutanocucurbit[6]uril, which was 3.3-fold higher.

The Cyclobutanocucurbit[5–8]uril Family: Electronegative Cavities in Contrast to Classical Cucurbituril while the Electropositive Outer Surface Acts as a Crystal Packing Driver

“…Previous reported decreases in binding affinity of guests cannot, therefore, be explained based on larger portals or spacious cavities; however, the electronic differences are a likely a factor [ 30 ].…”

“…A bank of fully substituted derivatives of Q[ n ] have slowly emerged in the literature between 1992–2017, where the equatorial regions have been decorated with methyl (Me), hydroxyl (OH) groups, or the fused rings cyclohexano (CyH), cyclopentano (CyP), and cyclobutano (CyB) ( Figure 1 , R n Q[ n ]) [ 25 , 26 , 27 , 28 , 29 , 30 ]. The alkyl-substituted examples are all synthesized by the H + /cat.…”

“…However, bearing Me or CyH substituents only favors the formation of the smaller homologues n = 5 (major) and 6 [ 25 , 26 , 27 ]. Significantly, the contracted rings, especially CyB, enable the formation of higher homologues n = 7 and 8 [ 29 , 30 ]. Just prior to our reporting of the synthesis of the fully substituted CyB 8 Q[8] the partially substituted Me 4 Q[8] and CyH 2 Q[8] were the only higher homologues ( n = 8) carrying substitution that are prepared by condensation and cyclo-oligomerization ( Figure 1 , bottom R x Q[ n ]) [ 31 ].…”

“…Herein, we report a repeat of the initial synthesis of CyB 5–8 Q[5–8] with the objective of obtaining crystal structures for each of the homologues [ 30 ]. This not only provides support for the original findings but also enables the collection of important structural data to better understand possible influences on their physical and chemical properties.…”

“…In solution, it was previously observed that equatorial substitution has an effect upon the binding affinities of various molecular guests, where affinities can increase or decrease relative to the same guest molecule [ 20 , 21 , 22 , 29 , 30 , 31 , 32 ]. In the case of partially substituted derivatives such as Me 4 Q[6] and Me 4 Q[8] ( Figure 1 , bottom), a distortion in the cavity can partly explain a change in the binding affinity, which is also dependent upon the guest’s shape [ 20 , 21 , 22 , 31 ], whereas, with full substitution, the Q cavities are spheroidal and effects upon binding affinities in solutions can best be explained by electronic changes, the degree of Q structure rigidity, and variations in diameters of the portals and cavities.…”